The c-abl oncogene is a ubiquitously expressed nonreceptor tyrosine kinase shown to have both nuclear and cytoplasmic functions. The objective of this research proposal is to study the role phosphorylation plays in the regulation of the subcellular localization of c-abl. The specific aims are: i.) To determine if c-abl contains a putative secondary NLS. The ability of this secondary NLS to direct nuclear targeting will be analyzed by mutation of this sequence in c- abl and by fusion of the putative NLS to a reporter protein. ii.) A functional analysis of the effects of phosphorylation of proposed NLS regulatory residues will he performed to determine if phosphorylation inhibits the nuclear targeting ability of the NLS. iii) The kinase pathway responsible for phosphorylation of the NLS regulatory residues will be characterized. The results of this proposal will contribute to the understanding of how c-abl subcellular distribution is regulated. This research may begin to elucidate the cytoplasmic function of the c- abl tyrosine kinase.